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  1. Article ; Online: Structural mechanism of CRL4-instructed STAT2 degradation via a novel cytomegaloviral DCAF receptor.

    Le-Trilling, Vu Thuy Khanh / Banchenko, Sofia / Paydar, Darius / Leipe, Pia Madeleine / Binting, Lukas / Lauer, Simon / Graziadei, Andrea / Klingen, Robin / Gotthold, Christine / Bürger, Jörg / Bracht, Thilo / Sitek, Barbara / Jan Lebbink, Robert / Malyshkina, Anna / Mielke, Thorsten / Rappsilber, Juri / Spahn, Christian Mt / Voigt, Sebastian / Trilling, Mirko /
    Schwefel, David

    The EMBO journal

    2023  Volume 42, Issue 5, Page(s) e112351

    Abstract: Human cytomegalovirus (CMV) is a ubiquitously distributed pathogen whose rodent counterparts such as mouse and rat CMV serve as common infection models. Here, we conducted global proteome profiling of rat CMV-infected cells and uncovered a pronounced ... ...

    Abstract Human cytomegalovirus (CMV) is a ubiquitously distributed pathogen whose rodent counterparts such as mouse and rat CMV serve as common infection models. Here, we conducted global proteome profiling of rat CMV-infected cells and uncovered a pronounced loss of the transcription factor STAT2, which is crucial for antiviral interferon signalling. Via deletion mutagenesis, we found that the viral protein E27 is required for CMV-induced STAT2 depletion. Cellular and in vitro analyses showed that E27 exploits host-cell Cullin4-RING ubiquitin ligase (CRL4) complexes to induce poly-ubiquitylation and proteasomal degradation of STAT2. Cryo-electron microscopy revealed how E27 mimics molecular surface properties of cellular CRL4 substrate receptors called DCAFs (DDB1- and Cullin4-associated factors), thereby displacing them from the catalytic core of CRL4. Moreover, structural analyses showed that E27 recruits STAT2 through a bipartite binding interface, which partially overlaps with the IRF9 binding site. Structure-based mutations in M27, the murine CMV homologue of E27, impair the interferon-suppressing capacity and virus replication in mouse models, supporting the conserved importance of DCAF mimicry for CMV immune evasion.
    MeSH term(s) Animals ; Humans ; Mice ; Rats ; Cryoelectron Microscopy ; Cytomegalovirus Infections/genetics ; Interferon-Stimulated Gene Factor 3, gamma Subunit/metabolism ; Interferons/metabolism ; Muromegalovirus ; STAT2 Transcription Factor/genetics ; STAT2 Transcription Factor/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Receptors, Interleukin-17/metabolism
    Chemical Substances 2,4-bis(N,N'-di(carboxymethyl)aminomethyl)fluorescein (3147-15-7) ; Interferon-Stimulated Gene Factor 3, gamma Subunit ; Interferons (9008-11-1) ; IRF9 protein, rat ; STAT2 protein, human ; STAT2 Transcription Factor ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Receptors, Interleukin-17
    Language English
    Publishing date 2023-02-10
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 586044-1
    ISSN 1460-2075 ; 0261-4189
    ISSN (online) 1460-2075
    ISSN 0261-4189
    DOI 10.15252/embj.2022112351
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1808: Show issues Location:
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    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 100: Show issues

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  2. Article ; Online: A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants.

    Pishesha, Novalia / Harmand, Thibault J / Rothlauf, Paul W / Praest, Patrique / Alexander, Ryan K / van den Doel, Renate / Liebeskind, Mariel J / Vakaki, Maria A / McCaul, Nicholas / Wijne, Charlotte / Verhaar, Elisha / Pinney, William / Heston, Hailey / Bloyet, Louis-Marie / Pontelli, Marjorie Cornejo / Ilagan, Ma Xenia G / Jan Lebbink, Robert / Buchser, William J / Wiertz, Emmanuel J H J /
    Whelan, Sean P J / Ploegh, Hidde L

    Proceedings of the National Academy of Sciences of the United States of America

    2021  Volume 118, Issue 44

    Abstract: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and ... ...

    Abstract The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (Spike
    MeSH term(s) Amino Acid Sequence ; Animals ; Antibodies, Neutralizing/biosynthesis ; Antibodies, Viral/biosynthesis ; Antigen-Presenting Cells/immunology ; CD8-Positive T-Lymphocytes/immunology ; COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/prevention & control ; COVID-19 Vaccines/administration & dosage ; COVID-19 Vaccines/immunology ; COVID-19 Vaccines/pharmacology ; Camelids, New World/immunology ; Female ; Histocompatibility Antigens Class II/immunology ; Humans ; Immunity, Cellular ; Immunity, Humoral ; Immunization, Secondary ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Transgenic ; Pandemics/prevention & control ; Recombinant Fusion Proteins/administration & dosage ; Recombinant Fusion Proteins/genetics ; Recombinant Fusion Proteins/immunology ; SARS-CoV-2/genetics ; SARS-CoV-2/immunology ; Single-Domain Antibodies/administration & dosage ; Single-Domain Antibodies/immunology ; Spike Glycoprotein, Coronavirus/administration & dosage ; Spike Glycoprotein, Coronavirus/genetics ; Spike Glycoprotein, Coronavirus/immunology
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; COVID-19 Vaccines ; Histocompatibility Antigens Class II ; Recombinant Fusion Proteins ; Single-Domain Antibodies ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2
    Language English
    Publishing date 2021-03-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2116147118
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1148: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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    This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

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